We have recently demonstrated that derivatives of a novel class of heterocyclic compounds, mesoionic purinone analogs, inhibit cyclic AMP phosphodiesterase. Because of the potential therapeutic application of phosphodiesterase inhibitors, especially in the treatment of cardiovascular diseases, we propose to further investigate this new class of compounds. A systematic synthesis of derivatives of these mesoionic compounds will be undertaken and their ability to inhibit cyclic AMP phosphodiesterase will be evaluated. Inhibition of cyclic GMP phosphodiesterase will also be examined. After the initial compounds have been prepared and evaluated, additional compound design and synthesis will be developed, concurrent with performance of the enzyme assays, in an attempt to optimize activity and enhance selectivity. Due to the demonstrated ability of these compounds to undergo ring-opening, they may be of interest as unique biochemical-pharmacological tools. They might act as latent acylating agents which could result in irreversible inhibition of phosphodiesterases. To this extent, time-dependent assays will be performed and the kinetics of ring-opening and other physico-chemical properties of these compounds will be investigated. The pharmacology of the new compounds will be examined: they will be tested for their in vitro and in vivo ability to relax vascular smooth muscle and for their effect on the contractile force of the heart.